WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406395
CAS#: 221244-14-0
Description: 1NM-PP1 is a potent Mutant Kinases Inhibitor.
MedKoo Cat#: 406395
Name: 1NM-PP1
CAS#: 221244-14-0
Chemical Formula: C20H21N5
Exact Mass: 331.1797
Molecular Weight: 331.41424
Elemental Analysis: C, 72.48; H, 6.39; N, 21.13
Synonym: 1NM-PP1; 1NM PP1; 1NMPP1l PP1 analog II.
IUPAC/Chemical Name: 1-(tert-butyl)-3-(naphthalen-1-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
InChi Key: GDQXJQSQYMMKRA-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H21N5/c1-20(2,3)25-19-17(18(21)22-12-23-19)16(24-25)11-14-9-6-8-13-7-4-5-10-15(13)14/h4-10,12H,11H2,1-3H3,(H2,21,22,23)
SMILES Code: NC1=C2C(N(C(C)(C)C)N=C2CC3=C4C=CC=CC4=CC=C3)=NC=N1
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | 1-NM-PP1 is a Src family kinases inhibitor with IC50s of 4.3 nM and 3.2 nM for v-Src-as1 and c-Fyn-as1, respectively. |
| In vitro activity: | Treatment of cells expressing Jak1WT/Jak3WT with IL-2 and 1NM-PP1, a prototype analog-sensitive kinase inhibitor, did not lead to reduced STAT5 phosphorylation indicating that the inhibitor did not affect Jak1WT or Jak3WT activity (left panel in Figure 3). Interestingly, treatment of cells expressing either AS-Jak1/Jak3WT or Jak1WT/AS-Jak3 with IL-2 and 1NM-PP1 led to a hyperphosphorylation of the respective analog sensitive Jak (lanes 3 and 6 in Figure 3). In addition, the trans-phosphorylation of Jak3 by AS-Jak1 and of Jak1 by AS-Jak3 was reduced by 1NM-PP1. Importantly, STAT5 phosphorylation was effectively inhibited by 1NM-PP1 in cells expressing AS-Jak1/Jak3WT but not in cells expressing Jak1WT/AS-Jak3 (lanes 3 and 6 in Figure 3) again indicating that specific inhibition of Jak3 kinase activity does not result in efficient abrogation of signal transduction initiated by the IL-2 receptor. Reference: Chem Biol. 2011 Mar 25;18(3):314-23. https://www.sciencedirect.com/science/article/pii/S1074552111000408?via%3Dihub |
| In vivo activity: | The contribution of the receptor tyrosine kinase, type 2 (TrkB) to the generation and maintenance of injury-induced persistent pain was evaluated. Wild-type mice and transgenic (TrkB(F616A)) mice that express mutant but fully functional TrkB receptors were studied. By injecting a small molecule derivative of the protein kinase inhibitor protein phosphatase 1 (1NM-PP1), it is possible to produce highly selective inhibition of TrkB autophosphorylation in adult mice, without interfering with the activity of other protein kinases. Oral administration of 1NM-PP1, at doses that blocked phosphorylation of TrkB in the spinal cord, had no effect in behavioral tests of acute heat, mechanical, or chemical pain sensitivity. However, the same pretreatment with 1NM-PP1 prevented the development of tissue- or nerve injury-induced heat and mechanical hypersensitivity. Established hypersensitivity was transiently reversed by intraperitoneal injection of 1NM-PP1. Although interfering with TrkB signaling altered neither acute capsaicin nor formalin-induced pain behavior, the prolonged mechanical hypersensitivity produced by these chemical injuries was prevented by 1NM-PP1 inhibition of TrkB signaling. These results suggest that TrkB signaling is not only an important contributor to the induction of heat and mechanical hypersensitivity produced by tissue or nerve injury but also to the persistence of the pain. Reference: J Neurosci. 2009 Apr 29;29(17):5508-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720992/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 46.75 | 141.06 | |
| DMF | 30.0 | 90.52 | |
| DMF:PBS (pH 7.2) (1:5) | 0.15 | 0.45 | |
| Ethanol | 2.0 | 6.03 |
The following data is based on the product molecular weight 331.41424 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Sugi T, Kato K, Kobayashi K, Kurokawa H, Takemae H, Gong H, Recuenco FC, Iwanaga T, Horimoto T, Akashi H. 1NM-PP1 treatment of mice infected with Toxoplasma gondii. J Vet Med Sci. 2011 Oct;73(10):1377-9. doi: 10.1292/jvms.11-0085. Epub 2011 Jun 16. PMID: 21685719. 2. Wang X, Ratnam J, Zou B, England PM, Basbaum AI. TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain. J Neurosci. 2009 Apr 29;29(17):5508-15. doi: 10.1523/JNEUROSCI.4288-08.2009. PMID: 19403818; PMCID: PMC2720992. 3. Haan C, Rolvering C, Raulf F, Kapp M, Drückes P, Thoma G, Behrmann I, Zerwes HG. Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors. Chem Biol. 2011 Mar 25;18(3):314-23. doi: 10.1016/j.chembiol.2011.01.012. PMID: 21439476. |
| In vitro protocol: | 1. Haan C, Rolvering C, Raulf F, Kapp M, Drückes P, Thoma G, Behrmann I, Zerwes HG. Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors. Chem Biol. 2011 Mar 25;18(3):314-23. doi: 10.1016/j.chembiol.2011.01.012. PMID: 21439476. |
| In vivo protocol: | 1. Sugi T, Kato K, Kobayashi K, Kurokawa H, Takemae H, Gong H, Recuenco FC, Iwanaga T, Horimoto T, Akashi H. 1NM-PP1 treatment of mice infected with Toxoplasma gondii. J Vet Med Sci. 2011 Oct;73(10):1377-9. doi: 10.1292/jvms.11-0085. Epub 2011 Jun 16. PMID: 21685719. 2. Wang X, Ratnam J, Zou B, England PM, Basbaum AI. TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain. J Neurosci. 2009 Apr 29;29(17):5508-15. doi: 10.1523/JNEUROSCI.4288-08.2009. PMID: 19403818; PMCID: PMC2720992. |
1: Cadou A, Couturier A, Le Goff C, Xie L, Paulson JR, Le Goff X. The Kin1 kinase and the calcineurin phosphatase cooperate to link actin ring assembly and septum synthesis in fission yeast. Biol Cell. 2013 Mar;105(3):129-48. doi: 10.1111/boc.201200042. Epub 2013 Feb 8. PubMed PMID: 23294323.
2: Liang H, Lim HH, Venkitaraman A, Surana U. Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest. EMBO J. 2012 Jan 18;31(2):403-16. doi: 10.1038/emboj.2011.385. Epub 2011 Nov 4. PubMed PMID: 22056777; PubMed Central PMCID: PMC3261552.
3: Sugi T, Kato K, Kobayashi K, Kurokawa H, Takemae H, Gong H, Recuenco FC, Iwanaga T, Horimoto T, Akashi H. 1NM-PP1 treatment of mice infected with Toxoplasma gondii. J Vet Med Sci. 2011 Oct;73(10):1377-9. Epub 2011 Jun 16. PubMed PMID: 21685719.
4: Haan C, Rolvering C, Raulf F, Kapp M, Drückes P, Thoma G, Behrmann I, Zerwes HG. Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors. Chem Biol. 2011 Mar 25;18(3):314-23. doi: 10.1016/j.chembiol.2011.01.012. PubMed PMID: 21439476.
5: Sugi T, Kato K, Kobayashi K, Watanabe S, Kurokawa H, Gong H, Pandey K, Takemae H, Akashi H. Use of the kinase inhibitor analog 1NM-PP1 reveals a role for Toxoplasma gondii CDPK1 in the invasion step. Eukaryot Cell. 2010 Apr;9(4):667-70. doi: 10.1128/EC.00351-09. Epub 2010 Feb 19. PubMed PMID: 20173034; PubMed Central PMCID: PMC2863409.
6: Zuin A, Carmona M, Morales-Ivorra I, Gabrielli N, Vivancos AP, Ayté J, Hidalgo E. Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway. EMBO J. 2010 Mar 3;29(5):981-91. doi: 10.1038/emboj.2009.407. Epub 2010 Jan 14. PubMed PMID: 20075862; PubMed Central PMCID: PMC2837171.
7: Wang X, Ratnam J, Zou B, England PM, Basbaum AI. TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain. J Neurosci. 2009 Apr 29;29(17):5508-15. doi: 10.1523/JNEUROSCI.4288-08.2009. PubMed PMID: 19403818; PubMed Central PMCID: PMC2720992.
8: Morgan DJ, Weisenhaus M, Shum S, Su T, Zheng R, Zhang C, Shokat KM, Hille B, Babcock DF, McKnight GS. Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20740-5. doi: 10.1073/pnas.0810971105. Epub 2008 Dec 12. PubMed PMID: 19074277; PubMed Central PMCID: PMC2634883.
9: Wang H, Feng R, Phillip Wang L, Li F, Cao X, Tsien JZ. CaMKII activation state underlies synaptic labile phase of LTP and short-term memory formation. Curr Biol. 2008 Oct 28;18(20):1546-54. doi: 10.1016/j.cub.2008.08.064. Epub 2008 Oct 16. PubMed PMID: 18929487; PubMed Central PMCID: PMC2628633.
10: Kim JS, Lilley BN, Zhang C, Shokat KM, Sanes JR, Zhen M. A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation. Neural Dev. 2008 Sep 22;3:23. doi: 10.1186/1749-8104-3-23. PubMed PMID: 18808695; PubMed Central PMCID: PMC2564922.
